Abstract
To investigate the effects of methylation of the p73 gene on the pathogenesis of non-Hodgkin lymphoma (NHL), the methylation status of the p73 gene promoter and the expression of p73 mRNA were examined in NHLs by methylation-specific polymerase chain reaction (MSP) and reverse transcription-polymerase chain reaction, respectively; p73 protein was detected by Western blotting analysis. Furthermore, the expression of p73 mRNA in NHL cells treated with 5-Aza-2′-deoxycytidine was analyzed. MSP results revealed that the promoter of p73 was methylated in 87.5% of NHLs but was not methylated in reactive hyperplasia lymph node samples. The expression of p73 mRNA was not detected in 83.33% of NHLs but was detected in all of the reactive hyperplasia lymph node samples. The p73 protein was not detected in 91.67% of NHLs but was detected in all of the reactive hyperplasia lymph node samples. The expression of p73 mRNA was detected in NHL cells treated with 5-Aza-2′-deoxycytidine. The inactivation of p73, predominantly by methylation, may be involved in the pathogenesis of NHLs.
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References
Fisher SG, Fisher RI. The epidemiology of non-Hodgkin’s lymphoma. Oncogene. 2004;23(38):6524–534.
Kok M, Bonfrer JM, Korse CM, de Jong D, Kersten MJ. Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin’s lymphoma. Tumor Biol. 2003;24(1):53–60.
Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997;90(4):809–19.
Dejeux E, Rønneberg JA, Solvang H, Bukholm I, Geisler S, Aas T, Gut IG, Børresen-Dale AL, Lønning PE, Kristensen VN, Tost J. DNA methylation profiling in doxorubicin treated primary locally advanced breast tumours identifies novel genes associated with survival and treatment response. Mol Cancer. 2010; 9:68.
Natarajan TG, Kallakury BV, Sheehan CE, Bartlett MB, Ganesan N, Preet A, et al. Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell Int. 2010;10:13.
Yao JY, Zhang L, Zhang X, Ma Y, He ZY, Hui LJ, et al. H3K27 trimethylation is an early epigenetic event of p16INK4a silencing for regaining tumorigenesis in fusion reprogrammed hepatoma cells. J Biol Chem. 2010;285(24):18828–37.
Feinberg AP, Tycko B. Timeline — The history of cancer epigenetics. Nat Rev Cancer. 2004;4(2):143–53.
Siu LLP, Chan JKC, Wong KF, Choy C, Kwong YL. Aberrant promoter CpG methylation as a molecular marker for disease monitoring in natural killer cell lymphomas. Br J Haematol. 2003;122(1):70–7.
Corn PG, Kuerbitz SJ, van Noesel MM, Esteller M, Compitello N, Baylin SB, et al. Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt’s lymphoma is associated with 5′ CpG island methylation. Cancer Res. 1999;59(14):3352–6.
Liu M, Taketani T, Li R, Takita J, Taki T, Yang HW, et al. Loss of p73 gene expression in lymphoid leukemia cell lines is associated with hypermethylation. Leuk Res. 2001;25(6):441–7.
Marabese M, Vikhanskaya F, Beoggini M. p73: a chiaroscuro gene in cancer. Eur J Cancer. 2007;43(9):1361–72.
Ramadan S, Terrinoni A, Catani MV, Sayan AE, Knight RA, Mueller M, et al. p73 induces apoptosis by different mechanisms. Biochem Biophys Res Commun. 2005;331(3):713–7.
Kovalev S, Marchenko N, Swendeman S, LaQuaglia M, Moll UM. Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines. Cell Growth Differ. 1998;9(11):897–903.
Garcia-Manero G, Daniel J, Smith TL, Kornblau SM, Lee MS, Kantarjian HM, et al. DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin Cancer Res. 2002;8(7):2217–24.
Galm O, Wilop S, Luders C, Jost E, Gehbauer G, Herman JG, et al. Clinical implications of aberrant DNA methylation patterns in acute myelogenous leukemia. Ann Hematol. 2005;84 (Suppl 1):39–46.
Roman-Gomez J, Jiminez-Velasco A, Castillejo JA, Agirre X, Barrios M, Navarro G, et al. Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood. 2004;104(8):2492–8.
van Doorn R, Zoutman WH, Dijkman R. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol. 2005;23(17):3886–96.
Siu LLP, Chan JKC, Wong KF, Kwong YL. Specific patterns of gene methylation in natural killer cell lymphomas: p73 is consistently involved. Am J Pathol. 2002;160(1):59–66.
Schmelz K, Wagner M, Dörken B, Tamm I. 5-Aza-2′-deoxycytidine induce p21(WAF) express by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia. Int J Cancer. 2005;114(5):683–95.
Wijermans PW, Lübbert M, Verhoef G, Klimek V, Bosly A. An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol. 2005;84(Suppl 1):9–17.
Kantarjian HM, O’Brien S, Cortes J, Giles FJ, Faderl S, Issa JP, et al. Results of decitabine (5-Aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer. 2003;98(3):522–8.
Yang AS, Doshi KD, Choi SW, Mason JB, Mannari RK, Gharybian V, et al. DNA methylation changes after 5-aza-2 ′-deoxycytidine therapy in patients with leukemia. Cancer Res. 2006;66(10):5495–503.
Link PA, Baer MR, James SR, Jones DA, Karpf AR. p53-inducible ribonucleotide reductase (p53R2/RRM2B) is a DNA hypomethylation-independent decitabine gene target that correlates with clinical response in myelodysplastic syndrome/acute myelogenous leukemia. Cancer Res. 2008;68(22):9358–66.
Roman-Gomez J, Agirre X, Jiménez-Velasco A, Arqueros V, Vilas-Zornoza A, Rodriguez-Otero P, et al. Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. J Clin Oncol. 2009;27(8):1316–22.
Vilgelm A, El-Rifai W, Zaika A. Therapeutic prospects for p73 and p63: rising from the shadow of p53. Drug Resis Updat. 2008;11(4–5):152–63.
Acknowledgments
This work was supported with the grants from the National Natural Science Foundation of China (no. 81071947, 30770906, and 30270750) and the Science Foundation from the Ministry of Education of China (no. 200805330049).
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Jing-Hong Pei and Sai-Qun Luo contributed equally to this publication.
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Pei, JH., Luo, SQ., Zhong, Y. et al. The association between non-Hodgkin lymphoma and methylation of p73 . Tumor Biol. 32, 1133–1138 (2011). https://doi.org/10.1007/s13277-011-0215-0
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DOI: https://doi.org/10.1007/s13277-011-0215-0